Accurate diagnostic of pulmonary diseases such as asthma or COPD is crucial to determine the appropriate treatment. Asthma and COPD are often misdiagnosed, and persons with COPD are treated instead for asthma and vice versa (ATS, 1995). In fact, primary care physicians revealed frequently prescribe similar medications for COPD and asthma even though the appropriate treatments differ (Kesten et al., 1993).
Severe asthma patients have frequent exacerbations and hospitalizations and account for over half of the cost of the disease and most of its mortality (Gaga et al., 2009). Inflammation, an important feature in severe asthma, exhibits different phenotypes that can be characterized by persistence of varying degrees of eosinophilic and neutrophilic infiltration (Balzar et al., 2002). The presence of eosinophils in asthma has been well documented via airway biopsy studies. The clinical importance of eosinophils in asthma has been demonstrated by the observation of frequent asthma exacerbations in patients who have sputum eosinophil counts >3%. Moreover, clinical trials designed to adjust inhaled anti-inflammatory therapy to maintain sputum eosinophil counts to <3% have resulted in fewer asthma exacerbations (Green et al., 2002). Symptomatic asthmatics with recalcitrant sputum eosinophilia on standard therapy have also improved after monoclonal antibody therapy (mepolizumab) that depletes airway eosinophils (Nair et al., 2009; Haldar et al., 2009).
To date the only accurate and reliable method to identify eosinophilic asthmatics has been limited to procurement of induced sputum samples from patients (Molfino, 2012). The sputum induction procedure is a tedious and complex process that requires skilled technicians and equipment that are not readily available in clinical practice. Even with these shortcomings, induced sputum remains the gold standard for assessing the cellular inflammatory processes that occur in asthma (Lieberman, 2007). A panel convened from the National Institutes of Health and federal agencies to propose biomarkers to assess disease progression and response to treatment has recommended 2% eosinophils in sputum as the cut-off for classifying patients as sputum eosinophilic asthmatics (Szefler et al., 2012).
Other less invasive and simpler tests such as exhaled nitric oxide (eNO), also referred to as Fraction of Exhaled Nitric Oxide (FENO), and peripheral blood eosinophils counts among others have been studied in an attempt to find an alternative predictive markers for sputum eosinophil counts (Turner, 2007; Lieberman, 2007). None of these potential predictive markers alone have been found to have a strong enough diagnostic value to be useful in the clinical setting (Stick, 2009).
In 2011, the American Thoracic Society (ATS) has issued issues guidelines on the use of fractional exhaled nitric oxide (FENO) to identify eosinophilic asthmatics. According to the ATS official guidelines, FENO>50 parts per billion (ppb) (>35 ppb in children) indicates eosinophilic inflammation and, in symptomatic patients, responsiveness to corticosteroids are likely (Dweik et al., 2011). However, a recent systematic review and meta-analysis about the tailoring of asthma treatment based on eosinophilic markers (exhaled nitric oxide or sputum eosinophils), concluded that tailoring of asthma treatment based on FENO levels was not effective in improving asthma outcomes in children and adults (Petsky et al., 2012). The same study also concluded that it was not practical to use either sputum analysis (due to technical expertise required) or FENO in everyday clinical practice (Petsky et al., 2012).
Accordingly, there is an unmet need for validated methods and tools that can be used to screen eosinophilic asthmatics for enrollment in clinical trials and in clinical diagnosis for prescribing appropriate medications. In addition, there is an unmet need for methods and tools to adequately classify patients suffering from pulmonary diseases in order to identify the appropriate therapies.